Rodent Behavioral Core: The Analysis of Behavior

National Institute Of Mental Health

Investigators

Linked publications & trials

Abstract

Behavioral neuroscience links systems-level circuitry to behavior, cognition and emotion and is thus critical for understanding the afflictions that affect neuropsychiatric patients. Linking cognitive changes in a behaving rat or mouse to targeted manipulations of neural circuitry requires the convergence of expertise from scientific fields inside and outside of neuroscience. In designing research projects to understand the anatomy, genetics, and pharmacology underlying the control of behavior, researchers must understand the nature of the task, its measurements, and how to interpret the data. Several steps lie between the design of the experiment and the behavioral output, including choice of task (e.g., operant vs mazes), how to train the animal (shaping vs conditioning), the type of surgical manipulation (ablation, cannulation, inactivation, stimulation, etc.), and the format of data for analysis (summary vs. trial-by-trial). Most neuroscience researchers who use standard off-the-shelf behavioral tasks are not experts in the psychology of behavior and must therefore rely on experts in the domain of cognition. Complex cognitive behavior in rodents is often gauged by measuring the pattern of behavioral responses in tasks that involve, for example, decision-making, attention, memory, rule learning, flexibility, discrimination, and problem solving. In these tasks, rats and mice typically indicate their decisions by nose-poking visual patterns on a touchscreen like an iPad, making nose-poke entries into a series of lit holes, or depressing an extended lever triggered by time or cues. Some cognitive functions extrapolated from animal behavior have positively informed our investigation of cognitive functions in humans. Such animal-to-human approaches (e.g., delayed response) have directed the design and development of analogous tests for use in humans (e.g., self-ordered working memory). Behavioral neuroscience has also benefitted in the opposite direction by means of human-to-animal approaches as in the case of extradimensionsal/intradimensional set shifting, a test based upon the principles of the human Wisconsin Card Sorting Task. Together, these advances in behavioral testing have been particularly useful in establishing the neuroanatomical and neurochemical pathology for specific cognitive deficits in a range of brain and behavior disorders. In addition to providing equipment, training and consulting for researchers interested in using rodents as models to investigate disorders of brain and behavior, one important goal for the rodent behavioral core (RBC) is to continue to design and develop cutting edge behavioral methods and applications while maintaining facility resources at a high level of utility for users at all levels of expertise. This requires constant maintenance and calibration of equipment, user education and interaction, and commitment to setting the standard as the best Rodent Behavioral Core facility in the world in terms of research quality. In the past year, we have supported labs of several principal Investigators from NIMH, as well as NINDS, NIA, NIDCD, NHGRI, NICHD, NIDCD, NEI, NHLBI, NIAID, and NCI to further their scientific goals. Since opening in 2017, over 50 labs have used the RBC facility with over 180 trainees. Over the past year, we custom designed and developed new tasks to measure various aspects of behavior including providing options for users to assess certain emotional behaviors such as defensive reactions that were more ethologically grounded. More recently, these tests have been redesigned to allow frame-by-frame analysis to provide a more refined behavioral output. We have also instituted a mechanism to record ultrasonic vocalizations from groups of rodent families to measure social communication as an index of emotion. Virtually every piece of equipment in the RBC including operant chambers, mazes and open testing arenas can be integrated with transistor-transistor logic (TTL) capability to interface with any TTL triggerable piece of equipment or software to enable optogenetic capability. The capability of optogenetic studies in the RBC has made it an invaluable resource for many users who do not have the equipment or expertise to establish the infrastructure in their own labs. Most recently, we integrated methods of fiber photometry calcium imaging with spatial mazes, operant chambers, and tests of emotional memory to enable scientists to detect changes of fluctuations in fluorescence in intracellular calcium, which serves an indirect indicator of neural activity. This required updating our operant control systems to enable liquid rewards as well as pellets. In the past year, we have also provided novel software and hardware for behavioral experiments. For example, we created a novel paradigm using custom hardware to test the perception of very dim light in mice with genetic defects affecting the retina. This involved integrating new LED arrays in operant boxes that were sensitive enough to measure vision detection thresholds. We have taken steps to ensure the validity and reliability of experiments conducted in the facility. First, we have improved several apparatuses to improve tracking and reduce experimental error. Second, we improved the lighting in each room to allow our users to set customized (but reproducible) lighting conditions to suit their experimental needs. This includes the addition of infrared (IR) illuminators and cameras to allow experimenters to observe animals in complete darkness. In addition to providing equipment resources, we have written custom code for several users to enable detailed levels of behavioral quantification or analyses for their experiments. For example, general motor activity data is usually indexed as duration and location of activity. With custom code, weve been able to provide researchers with additional measures such as speed of activity as well as visual patterns of movement. We have also expanded our ability to provide sophisticated pose estimation methods that use deep learning models. This is an open-source code computer vision technique to accurately track an animals location as well as individual body parts. We are currently working on expanding this approach by integrating 3-dimensional imaging to capture stereoscopic effects (i.e., depth perception). This type of analysis allows us to detect and track animal behavior in 3-dimensional space. Our automated behavioral testing systems provide rich data that requires a great deal of time and effort to analyze and interpret. In the past year, we have created data processing pipelines for several of these systems such that users can easily obtain usable statistics and figures using code written by RBC staff. Its major advantage is that it allows the user to go directly from the data set creation to automatic behavioral analysis. It also provides a means to standardize behavioral testing in an open-access manner so that data generated in the RBC can be shared between collaborators. Finally, we have modernized much of our aging fleet of computers to make them faster, more reliable, and have the capacity to connect with a broader array of equipment. In the past fiscal year, the scientific support provided by the NIMH RBC has contributed to several peer reviewed articles published in Cerebral Cortex (Ma et al), Human Molecular Genetics (Zhu et al), Cell Reports (Beier et al), Nature Communications (Liu et al., Zhang et al) Nature Neuroscience (Ma et al), Journal of Comparative Neurology (Beier et al). Others are in a preprints stage located on BioRxiv (Jiang et al) and Research Square Ji et al), or currently in revision for Journal Neuroscience (Messanvi et al) and Brain (Wlaschi et al).